The aim of this retrospective study was to investigate whether rituximab can enhance the response rates to chemotherapy and even the survival outcomes of naïve PCNSL patients in Southern China. The primary endpoint of this report was objective response rate to RMT versus MT treatment in PCNSL. Secondary endpoints included, progression-free survival (PFS), overall survival (OS), and safety.

Study design

N = 62 previously-untreated PCNSL patients with no other involvement other than the CNS and pathologically diagnosed as diffuse large B-cell lymphoma (DLBCL)

Median patient age (range): 53.5 (29–77) years

Male patients: 51.6%

Dosing (regimen was repeated every three weeks; up to 6–8 cycles):

MT (n = 30):

Methotrexate: 3.5 g/m2 intravenously (IV) administered on Day 1

Every methotrexate dose, after 12 hours was followed by 30 mg leucovorin every six hours until methotrexate levels were < 1x10-7 mol/l

Temozolomide: 150 mg/m2 orally administered on Day 1–5

RMT (n = 32):

Methotrexate: 3.5 g/m2 intravenously (IV) administered on Day 1

Every methotrexate dose, after 12 hours was followed by 30 mg leucovorin every six hours until methotrexate levels were < 1x10-7 mol/l

Temozolomide: 150 mg/m2 orally administered on Day 1–5

Rituximab: 375 mg/m2 IV on Day 0

Treatment responses were assessed by contrast-enhanced magnetic resonance imaging (MRI), which was performed at baseline and after cycle 2, 4, and 6 of chemotherapy

Except for gender, the rest of the baseline characteristics were well balanced between the RMT and MT patient groups (RMT males: 65.6%; MT males: 36.7%; P = 0.041)

Key results

Response rates per treatment group (n = 61 evaluable patients):

RMT group (n = 32):

Overall response rate (ORR): 93.7% (n =30)

Complete response (CR): 53.2% (n = 17)

Partial response (PR): 40.6% (n = 13)

Progressive disease (PD): 3.1% (n = 1)

Stable disease (SD): 3.1% (n = 1)

MT group (n = 29):

ORR: 69.0% (n = 20)

CR: 27.6% (n = 8)

PR: 4% (n = 12)

PD: 24.1% (n = 7)

SD: 6.9% (n = 2)

The percentage of patients achieving CR with RMT was significantly higher than that with MT treatment (P < 0.001)

The percentage of patients achieving PR with RMT was not significantly different than that with MT treatment (P = 0.572)

The RMT regimen led to a significant higher ORR than MT treatment (P = 0.018)

Median follow-ups per group:

RMT: 13.7 months

During this time, six patients relapsed but with no extra CNS involvement

MT: 15.5 months

During this time, ten patients relapsed but with no extra CNS involvement

Two-year PFS rate:

RMT: 81.3%

MT: 46.5%

Five-year PFS rate:

RMT: 53.3%

MT: 29.1%

Comparison: P = 0.019

Two-year OS rate:

RMT: 82.3%

MT: 65.7%

Five-year OS rate:

RMT: 82.3%

MT: 50.0%

Comparison: P = 0.015

Median PFS:

RMT: not reached

MT: 25.3 months

Median OS:

RMT: not reached

MT: not reached

Multivariate analysis revealed that only treatment approach was an independent prognostic factor for OS (after age and gender adjustment)

Compared to MT, the RMT regimen reduced the risk of progression by 75% and then risk of mortality by 81.9%

Safety

No deaths due to drug toxicity were observed

Febrile neutropenia occurred in:

RMT: 9.4% (n = 3) of patients

MT: 6.7% (n = 2) of patients

Comparison: P = 1.00

Grade 1–2 hepatotoxicity was observed in:

RMT: 40.6% (n = 13) of patients

MT: 40% (n = 12) of patients

Comparison: P = 1.00

Grade 1–2 nausea vomiting was observed in:

RMT: 46.6% (n = 14) of patients

MT: 62.5% (n = 18) of patients

Comparison: P = 0.049

Grade 3–4 hematological adverse events (AEs) like anemia, neutropenia, and thrombocytopenia were not frequently observed in either group (P > 0.05)

Grade 3–4 non-hematological AEs were generally uncommon in both groups

Consolidation therapy in the form of whole-brain radiation was given to 32.3% of patients and as autologous stem cell transplantation to 3.2% of patients

Conclusions

In this retrospective analysis, RMT showed great efficacy, survival outcomes and tolerable toxicity when compared to MT. Thus, the authors suggest that RMT might be a feasible and safe therapeutic approach as a first‐line treatment for PCNSL. The results of this retrospective study although promising, they need to be further validated by large prospective studies to ensure the efficacy and safety of RMT in PCNSL.

Mar 15, 2019

Mar 12, 2019

Mar 1, 2019

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